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A quarter of the cardiac output is consigned to the perfusion of the kidneys - even though the kidneys amount to just 0.5 % of the total body weight. Approximately every 20 minutes, i.e. 70 times a day, the entire blood plasma is filtered by the kidneys. Therefore, kidney glomeruli are target organs for every hematogenous infection. Viral infection can cause primary glomerulonephritis, whereas an immune reaction can lead to secondary glomerulonephritis. HIV infection, hepatitis B and C as well as bacterial infections are all typical causes of renal disease. Nephrotoxic agents precipitate renal diseases that affect the interstitium and the tubular apparatus in particular, and we will have to deal with this increasingly in the era of HAART.

Nephroprotection

In view of the prolonged use of antiretroviral medication, long-term renal side effects are to be expected. Similar to experiences with diabetes mellitus and diabetic nephropathy, the principles of therapy should be particularly emphasized: adjustment of blood pressure values to < 130/80 mm Hg and no smoking. However, they have not yet been scientifically investigated in relation to HIV infection. The consequent adjustment of diabetes mellitus or change of therapy to avoid a metabolic syndrome are in principle advantageous and will probably have a long-lasting positive side effect on renal function.

On the basis of current data, the viral changes of the glomeruli and the renal tubules due to HIV infection should be reason enough to start/maintain an antiretroviral therapy in a symptomatic patient, rather than to worry too much about potential nephrotoxic side effects.

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Clinical manifestation/diagnosis of nephropathy The major symptoms of glomerulonephritis are proteinuria and "nephritic sediment". Clinically, a difference is made between nephrotic syndrome (loss of protein), acute nephritic syndrome (acantocytes as a sign of GN), rapid-progressive GN (loss of renal function in only a few days), asymptomatic proteinuria or hematuria and chronic GN.These entities are all treated differently and require the collaboration of a nephrologist. HIV-associated nephropathy (HIV-AN) is a form of glomerulonephritis and is diagnosed in cases of nephrotic syndrome with edema, hypoalbuminemia, hyperlipidemia and proteinuria of more than 3.5 g/day. However, even a mild proteinuria is possible. The occurrence of proteinuria and erythrocyturia is pathognomonic for glomerulonephritis (GN) and, together with a nephritic sediment, usually confirms the diagnosis. Under a polarizing microscope, a trained eye can easily identify the renal (glomerular) origin of the erythrocytes, on the basis of glomerularly deformed acanthocytes. More than 5 acanthocytes per field of vision is a significant sign for GN. Extensive erythrocyturia (bleeding) below the renal pelvis (tumor of the urinary tract collection system?) can be excluded by sonography and, if necessary, by cystoscopy. The clinical symptoms are determined by the extent of proteinuria with loss of protein and imbalance, as well as loss of renal function. The severity of edema, tiredness, reduced performance, susceptibility to infections, hyperlipidemia, anemia, metabolic acidosis, problems with the calcium-phosphate metabolism, as well as venous thrombi and newly diagnosed arterial hypertension is limited by the length and intensity of the renal insufficiency. An increase in serum creatinine is not to be expected until the glomerular filtration rate (GFR) is below 50 %, and should be identified early by clearance measurements. As a urine collection over two 24-hour periods is difficult to organize, three methods are generally used for estimating the clearance. 1. Formula according to Cockroft and Gault: 140-age x kg body weight) divided by (serum creatinine mg/dl x 72). For women, the result is multiplied by 0.85. 2. MDRD formula: this is more precise and only requires laboratory data (creatinine, urea, age and gender). The formula is as follows: creatinine clearance (MDRD) = 170 x Krea [mg/dl]-0.999 x age -0.176 x (urea [mg/dl] x 0.46]-0.170 x albumin [g/dl]-0.318 (for women: x 0.762) 3. Cystatin C clearance: cystatin C is a low molecular weight protein which is constantly generated by the organism, is filtered freely and regardless of gender, muscle mass, age with a minor intraindividual variability (< 5%) can serve as a marker for the creatinine value "blind range". However, determination is by no means inexpensive. The formula is: GFR (ml/min//1.73m2) = 78 x 1/CysC (Mg/l) + 4 or: 87 x 1/CsyC (mg/ml) - 6.9 Interstitial nephropathy, especially when caused by indinavir, can present as a sterile leukocyturia, and can also lead to a loss of renal function. Leukocyturia must be microbiologically clarified (culture of mid-stream urine) in order to initiate treatment with antibiotics according to the resistance situation, whereby a case of bacterial interstitial nephritis may also be in existence. Tuberculosis of the urinary tract should be considered as a possible cause of abacterial leukocyturia. The symptoms of drug-induced Fanconi's syndrome (tubulotoxic damage) are glucosuria + phosphaturia with a normal blood glucose (dropping the renal glucose limit) + hypophosphatemia. The patient feels tired and peaky, the symptoms are non-specific and an increase in serum creatinine is often delayed. Routine tests for renal impairment The routine investigation of an HIV-infected person should include tests for sodium, potassium, calcium, phosphate (every three months) and creatinine (creatinine clearance). The urine should be tested for glucosuria, proteinuria, erythrocyturia and leukocyturia every 3 months. If there is a significant rise in proteinuria or serum creatinine, a nephrologist should be consulted (renal biopsy if necessary).. There is no time to waste in the case of a rapid increase of creatinine (rapid-progressive glomerulonephritis?), an increase of LDH connected with hyperbilirubinemia and thrombocytopenia (hemolytic uremia syndrome, HUS), or severe electrolyte imbalance (especially hyperkalemia), or acidosis that cannot be controlled, which can also occur on therapy as lactacidosis. An asymptomatic, slight proteinuria with no rise in creatinine can be treated in almost one third of untreated patients and should be monitored quarterly. A decrease in renal function in patients with an HIV infection could be interpreted as a symptomatic HIV infection, and antiretroviral therapy might be considered. The use of a contrast medium (CM) for the urinary tract should be avoided, especially in cases of renal insufficiency, proteinuria and all forms of low intravasal volume (including cirrhosis of the liver), in order to avoid causing CM-induced renal failure. HIV-associated nephropathy (HIV-AN) HIV-AN is characterized by rapid loss of renal function, which is especially observed in Afro-Americans. At the end of 2005, 56 HIV-positive dialysis patients were registered in Germany (new in 2005: 9 dialysis patients with HIV and 3 HIV patients with a kidney transplant, Quasi Kidney Report 2006). The risk factors are genetic predisposition (97 % Afro-Americans), male gender and drug abuse. Most patients have a poor immune status with < 100 CD4+ T-cells/µl (only 20 % have normal ranges). Individual cases of sudden renal insufficiency within an acute HIV syndrome have been reported. But there seems to be no correlation with HIV viral load and the duration of the HIV infection. Nephrotic proteinuria usually presents clinically as more than 3.5 g/day, but a minor proteinuria is also possible. Progression is fast and can lead to end-stage renal disease (dialysis) in less than 10 months (Szczech 2001). The blood pressure is normal or slightly increased; the kidneys are within the normal size range when examined by ultrasound scan. Despite hemodialysis, the one-year-mortality rate is 50 %; on antiretroviral therapy it still reaches around 30 %. The histological findings in biopsies mostly (70 %) correspond to a focal segmental sclerosing glomerulonephritis (FSGN), which is also frequently observed in "malignant hypertension" in Afro-Americans. However, other causes of a glomerulonephritis, such as an amyloid kidney are also possible with HIV (Daugas 2005). Single case descriptions with the histological course of disease have confirmed the direct infection of the glomerular basal membrane with HIV, and have documented an impressive positive effect of HAART on the histological changes (Winston 2001). Experience with other FSGN-forms has shown that only early intervention with HAART - before scarring of the glomeruli occurs due to the underlying disease - has a chance of success. This calls for a rapid reaction: HIVAN is independent from CD4 cell count and viral load must be treated.. The use of components of antiretroviral therapy should take into consideration the different means of renal elimination (adaptation of the dosing). ACE-inhibitors (captropil 6.25 to 25 mg bid, then change to a longer-term effective preparation such as enalapril 5 mg) should be added (see also Table 2). The use of steroids is the subject of controversial discussion (1 mg/kg KG/day for 2 to 11 weeks), but is favoured in the USA alongside initiation of a HAART, particularly in cases which take a course similar to lupus (Haas 2005, Gupta 2005). Post-infectious glomerulonephritis Many bacteria and viruses are able to trigger or support an acute post-infectious glomerulonephritis or other forms of chronic GN. Viral infections such as CMV, EBV, VZV, influenza, adenovirus, and parvovirus B19 do this as well as HIV. After syphilis and infections with staphylococci, pneumococci, legionella, salmonelli and other infectious agents, an acute post-infectious glomerulonephritis can also occur. An acute HIV infection can cause renal insufficiency. Membranous glomerulonephritis is a special form of secondary glomerulonephritis, which can appear in malignant tumors and hepatitis (B and C). Chronic hepatitis C can lead to a membrano-proliferative GN, or through cryoglobulinemia can also cause vasculitis with renal involvement. The most common form of renal disease in Germany is IGA nephropathy, which can also be triggered by an HIV infection, respiratory infections or infection with Hepatitis A. Post-infectious GN is treated specifically (see below); the underlying infection is treated simultaneously. Irrespective of the liver histology, hepatitis C-associated GN can also be a reason for therapy with interferon/ribavirin (observe adaptation of the dosing intervals). However, ribavirin shouldn't be used if the creatinine clearance is less than 50 ml/min/1.73 m² because of the danger of prolonged anemia. In the case of a nephritic syndrome as a result of cryoglobulin anemia in hepatitis C, a low-dosage interferon maintenance therapy or other anti-inflammatory anti-lymphocyte therapy should be considered. Principles of therapy of glomerulonephritis The underlying cause of a post-infectious glomerulonephritis should be treated first, including hepatitis B, C and HIV infection. Particular attention should be paid to the adjustment of blood pressure: target values are < 130/80 mm Hg or, in the presence of proteinuria < 120/80 mm Hg. ACE-inhibitors as well as AT-II-receptor-antagonists are used to control blood pressure, usually in combination with diuretics. Proteinuria should be treated with an ACE-inhibitor, also at high doses, if necessary, irrespective of the blood pressure, and should be combined additionally with AT-II-receptor-antagonists if the proteinuria is more than 0.5 to 1 g/day. The protein intake is reduced to 0.6-0.8 g/kg/day (low protein diets like the Mediterranean diet might be helpful). Fluids should be restricted to 1.5 to 2 l/day and adapted according to the body weight and amount of edema. Forced drinking of large amounts, or rather the alleged "flushing" of the kidneys or the use of high-ceiling diuretics in combination with increased fluid flow rate, has no effect on renal function. Not smoking is of vital importance because nicotine causes an increase in the risk of progression of glomerulonephritis. Hyperlipidemia should be treated after dietary arrangements have been exhausted. HMG-CoA reductase inhibitors are ideal, provided that they can be combined with the antiretroviral therapy (see chapter on drug interactions). Fibrates or fibrates in combination with statins may only be used carefully when renal function is reduced (cumulation). Analgesics should be waived as far as possible, which applies especially to the "small" analgesics, such as ASA and paracetamol. ,When the creatinine clearance reaches a value of less than 50 ml/min/1.73 m², at the latest, treatment should be managed by a nephrologist. Treatment of hypertension Please take note of the specific side effects of antihypertensive drugs. Note hyperkalemia with ACE-inhibitors; at a creatinine count of 1.4 mg/dl do not use potassium-saving diuretics; at creatinine > 1.8 mg/dl high-ceiling diuretics such as furosemid or torasemid should be used. Table 1: Blood pressure adjustments Category Drug Dosage (examples) ACE-inhibitors Lisinopril, Benazepril-HCL, Fosinopril sodium, Enalapril, etc Fosnormâ 5 mg (1 x morning, increase slowly to 20 mg/day Beta-blockers Metoprolol, Bisoprolol Beloc-Zokâ (mite) 1x1 AT I-receptor- antagonists Valsartan, Candesatan, Telmisartan, etc. Blopressâ first 2-4 mg/day, increase carefully to 16 mg/day Diuretics Hydrochlorothiazide + Triamterene Dytide Hâ 1x1 Ca-antagonists Amlodipine Norvascâ 5 mg 1x1, after > 1 week increase to 2x1 if necessary Renal safety of antiretroviral therapy The spectrum of an allergic or autoimmune reaction in the kidney is no different from the skin or other internal organs. Reactions can be humoral or T-cell-mediated and can lead to renal insufficiency. The spectrum ranges from the type I immune reaction (acute interstitial nephritis after exposure to medication) to the type IV T-cell-mediated reaction (special forms of a chronic interstitial nephritis). It is, therefore, important to know that even the one-off use of an analgesic (e.g. ibuprofen) can lead to renal failure. In principle, this is possible with antiretroviral drugs. Any change of treatment should be followed by a check of renal function, after 14 days in the case of any noticeable renal changes, otherwise every 4 weeks in the first year. Acute renal failure or acute tubular necroses can also occur during treatment with aciclovir, ganciclovir, adefovir, aminoglycosides or pentamidine. Tubular dysfunctions may also be found with DDI, D4T or 3TC. An acute allergic interstitial nephritis can arise in connection with a hypersentitivity reaction when taking ABC. With patients taking atazanivir and T-20, membranoproliferative glomurelonephritides were observed. The typical side effects of antiretroviral therapy are: Indinavir-associated nephropathy In the indinavir doses used in the past,. the cumulative occurrence of the symptomatic nephrolithiasis was indicated to be over 10 %. .The renal side-effects ranged from asymptomatic crystalluria to renal failure.. Renal problems have become rarer with the boosted doses used today On abdominal x-ray, an indinavir stone is not usually apparent. However, in combination with calcium it can become radio-opaque, and could be confused with a calcium-oxalate-stone. Urate stones are transparent on x-rays. When evaluating the triggering agent, it must be observed that other medicaments could have caused the crystalluria, and only resulted in nephrolithiasis on combination with indinavir (e.g. ampicillin, acyclovir, aspirine, ciprofloxacin, methotrexate, vitamin C, sulfonamide and also other drugs that lead to an increase in uric acid). Elevation of creatinine under long-term indinavir therapy was already observed at the end of the 90s (Fellay 2001, Boubaker 2001). Typical signs of indinavir nephropathy include sterile leukocyturia and an echogenic transformation of the renal parenchyma in otherwise normal kidneys. Discontinuing indinavir leads to a normal function in most cases. One should pay heed to the possibility of tuberculosis in the urinary tract in sterile leukocyturia. Tubulotoxic damage, Fanconi's syndrome When the substances filtered from the glomerulum in primary urine exceed the transport capacity of the reabsorbing tubular cells, they are excreted with the urine. The most prominent example is the glucose threshold of the kidneys (180 mg/dl). However, a transport dysfunction in the tubular system can also be caused by drugs such as cidofovir, tenofovir and adefovir. This is then known as a secondary (drug-induced) Fanconi's syndrome and is distinguished by a malfunction of the tubular system without there necessarily being any impairment of the GFR. There is an increased amount of phosphate, amino acids and glucose in the urine, whereas phosphate in the blood is reduced. The loss of amino acids, phosphate, glucose, bicarbonate and other organic and inorganic substances, as well as water, can become clinically manifest in the form of increased urination, thirst or tiredness. In case reports, renal failure was above all described in patients with other reasons for renal insufficiency, mostly under boosted PI-regimes with tenofovir as well as secondary disorders and cirrhosis of the liver or hepatitis. Nephrologists advise caution in selecting antiretroviral therapy for patients with proteinuria, nephritic syndrome, cirrhosis of the liver, and/or dyslipoproteinemia. Nephrotoxic substances such as cidofovir, adefovir and tenofovir should be avoided in these patients. In principle, it is possible to administer NRTIs, and a regime of only two boosted PIs can be given "as a kidney-neutral solution" in individual cases For patients with healthy kidneys, there are no restrictions at present. However, careful monitoring of serum creatinine, proteinuria, erythrocyturia and serum phosphate can only be recommended. Tenofovir and the kidney . In view of the broad application of tenofovir, more attention must be devoted to long-term renal toxicity in the future. Based on 455,392 patient years, the incidence of unwanted renal occurrences at Gilead since drug approval amounted to 29.2 renal events per 100,000 patient years (Nelson 2006). However, unreliable notification performance means that this is not a realistic reflection of the true situation. The leading renal event when taking tenofovir is Fanconi's syndrome (Incidence: 22.4/100,000 patient years).This was almost always diagnosed in conjunction with hypophosphatemia, glucosuria (renal diabetes mellitus with normal blood sugar), and a mild proteinuria. It occurs on average 7 months after beginning intake and disappears 4 to 8 weeks after discontinuing. (Izzedine 2004). An isolated case of hypophosphatemia without glucosuria in HIV cannot yet be defined as Fanconi's syndrome and can just as well be due to malnutrition, vitamin D deficiency, diuretics or alcohol and doesn't necessarily mean tenofovir must be discontinued. In the accreditation studies, the incidence of renal events (changes in creatinine clearance, glucosuria, proteinuria, hypokaliemiam acidosis) when taking tenfovir was no higher than in the control groups. With patients treated previously, however, hypophosphatemia was observed in 13% after 24 weeks (113 weeks: 22%). This was more often than in the placebo arm, but not associated with other tubulotoxic symptoms (Gallant 2004 + 2006). The median time up to the occurrence of renal side-effects amounted to 9 months in a study (Izzedine 2004). The risk in increased through the combination with nephrotoxic substances, kidney disease or renal insufficiency in the patient's history, sepsis, dehydration, extremely advanced HIV disease or severe hypertension (Nelson 2006). Like the other NRTIs, tenofovir is eliminated renally and must be dose-.adapted in cases of renal insufficiency. Contrary to earlier case studies and the fact that ritonavir increases the Cmax and the AUC of tenofovir by about 30%, however, combination with boosted PIs is possible. This is also confirmed by in-vitro studies (Izzedine 2005, Ray 2005). In the first year of treatment with tenofovir, patients with healthy kidneys should be monitored monthly, thereafter every three months. Patients with kidney dysfunctions are monitored more often. In the case of additional nephrotoxic substances or drugs which are also excreted via the renal transporter ( aminoglycosides, amphotericin B, famciclovir, ganciclovir, pentamidine, vancomycine, cidofovir, IL-2), the renal function is monitored at weekly intervals. Dosage of antiretrovirals in renal insufficiency In each case, the technical information of the individual substances must be taken into consideration. Because NNRTIs and PIs are almost exclusively hepatically eliminated, a dose rate adjustment is normally only necessary for the NRTI, unless a coexistent insufficiency of the liver is present. Within the scope of hepatitis C therapy, ribavirin should be omitted in patients with renal insufficiency (note: prolonged anemia) if the creatinine clearance is under 50 ml/min/1.73 m². T-20 (Fuzeon™) can be used up to an endogenous creatinine clearance of 30 ml/min/1.73 m² without dose reduction; no data is available for more severe renal insufficiency. Table 2: Dosage of antiretroviral medicaments in renal insufficiency (in each case diurnal dosages, if not otherwise stated) HD=Hemodialysis Category Standard dose CrCl (ml/ min) Dose in renal insufficiency AZT (Retrovir®) 2 x 250 mg > 10 < 10 2 x 250 mg 300 - 400 mg 3TC (Epivir®) 1 x 300 mg or 2 x 150 mg > 50 30 - 49 < 30 < 5 Standard dose 1 x 150 mg 150 mg (15 ml) on day 1; 100 mg (10 ml)/day thereafter 50 mg ( 5 ml) on day 1; 25 mg (2,5 ml)/day thereafter AZT+3TC (Combivir®) 2 x 1 Tabl. > 50 < 50 Standard dose Not recommended ABC (Ziagen®) 2 x 300 mg > 50 < 50 Standard dose contraindicated AZT/+3TC+ABC (Trizivir®) 2 x 1 Tabl. > 50 < 50 Standard dose Not recommended d4T (Zerit®) 2 x 40 mg (> 60 kg) 2 x 30 mg (< 60 kg) > 50 30 - 49 < 30 Standard dose half standard dose quarter standard dose ddI (Videx®) 1 x 400 mg (> 60 kg) 1 x 250 mg (< 60 kg) (combined with TDF never exceed 1 x 250 mg) > 60 30 - 59 10 - 29 < 10 Standard dose half standard dose 1 x 150 or 100 mg 1 x 100 or 75 mg TDF (Viread®) 1 x 245 mg >50 30 - 49 10 - 29 HD patients Standard dose 245 mg every 2 days 245 mg every 72-96 h 245 mg every 7 days past HD FTC (Emtriva®) 1 x 200 mg > 50 30 - 49 15 - 29 < 15 (incl. HD) Standard dose 200 mg every 2 days 200 mg every 72 h 200 mg every 96 h TDF (Truvadaâ) 1 x 1 tablet > 50 30 - 49 y 30 and HD Standard dose every 24 h 1 tabl. Every 48 h Not recommended OIs and renal insufficiency Pneumocystis pneumonia As cotrimoxazole is nephrotoxic as a high-dose therapy, its use must be carefully considered. Systemic administration of pentamidine should also be avoided in patients with renal insufficiency. Table 3: PCP treatment in renal insufficiency GFR normal GFR >50 ml/min GFR 10-50 ml/min GFR <10 ml/min Dose adaptation for HD/CAPD/cont. NET *Cotrimoxazole 960 mg 3 x 3/die (total of 120 mg/ kg daily) (100 % every 12 h) (100 % every 12-24 h) (50 % every 24 h) HD: + half dose after dialysis CAPD: no adaptation CAVH: GFR 10-50 CVVHD: GFR < 10 Dapsone 100 mg every 24 h 50-100 % 50 % avoid avoid Atovaquone 750 mg every 12 h 100 %** 100 %** 100 %** HD: no adaptation CAPD: no adaptation* CAVH: (GFR < 10)** Pentamidine 4 mg/kg every 24 h 100 % 100 % every 24-36 h 100 % every 48 h see text !!! HD: (GFR < 10)*** CAPD: (GFR < 10)** CAVH: (GFR < 10)** * no studies available, normal dosage recommended, ** no studies available, dosage as for GFR < 10ml/min recommended. (cont. NET = continuous dialysis, HD = intermittent hemodialysis, CAPD = continuous ambulant peritoneal dialysis; CAVH = continuous arterio-venous hemofiltration, CVVHD = continuous veno-veno hemodiafiltration). Toxoplasmosis encephalitis Table 4: Treatment of cerebral toxoplasmosis with renal insufficiency GFR normal GFR > 50 ml/min GFR 10-50 ml/min GFR < 10 ml/min Dose adaptation for HD/CAPD/cont. NET Pyrimethamine 50-75 mg every 24 h 100 % 100 % 100 % HD: no adaptation CAPD: no adaptation CAVH: no adaptation Clindamycin 150-300 mg every 6 h 100 % 100 % 100 % HD: no adaptation CAPD: (GFR < 10)* CAVH: (GFR < 10)* CVVHD: GFR normal Sulfadiazine 2 g every 6 h Avoid Avoid Avoid Avoid *= no studies available, dosage as for GFR < 10 ml/min recommended. (cont. NET = continuous dialysis, HD = intermittent hemodialysis, CAPD = continuous ambulant peritoneal dialysis; CAVH = continuous arterio-venous hemofiltration, CVVHD = continuous veno-veno hemodiafiltration). CMV, HSV, VZV infection Table 5: Treatment of CMV, HSV, VZV in renal insufficiency Drug GFR normal GFR > 50 ml/min GFR 10-50 ml/min GFR < 10 ml/min Dose adaptation for HD/CAPD/cont. NET Acyclovir 5-10 mg/kg every 8 h 5 mg/kg every 8-12 h 5 mg/kg every 12-24 h 2.5 mg/kg every 24 h HD: Dose after dialysis CAPD: GFR < 10 CAVH: 3.5 mg/kg every 24 h CVVHD: 6.5-15 mg/kg every 24 h Ganciclovir 5 mg/kg every 12 h 3 mg/kg every 12 h if GFR 25-50 ml 3 mg/kg every 24 h if GFR 10-25 ml 15 mg/kg every 24 h HD: Dose after dialysis CAPD: GFR < 10 CAVH: 3.5 mg/kg every 24 h CVVHD: 2.5 mg/kg every 24 h Valgan-ciclovir 900 mg every 12 h GFR 40-59 ml/min 450 mg every 12 h GFR 25-39 ml/min 450 mg every 24 h GFR 10-24 ml/min 450 mg every 48 h for induction unknown unknown Foscavir 90 mg/kg every 12 h 50-100 % 10-50 % avoid HD: Dose after dialysis CAPD: 60 mg/kg every 48-72 h CAVH: GFR 10-50 Cidofovir 5 mg/kg every 7 days 100 % 0.5-2 mg/ kg every 7 days avoid HD: GFR 10-50 CAPD: GFR 10-50 CAVH: avoid Famciclovir 250 mg every 8 h p.o. Every 12 h Every 48 h 50 % every 48 h HD: Dose after dialysis CAPD: ? CAVH: GFR 10-50 (cont. 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